ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016

Inclusion Criteria:

• Down syndrome diagnosed clinically or cytogenetically (including Mosaic Down)
• Newly diagnosed ALL according to WHO 2016 classification.
• Age < 21 years old at time of enrollment.
• ECOG performance status (PS) score of 0-2.
• Written informed consent obtained from legally acceptable representatives.

Exclusion Criteria:

• Second malignancy.
• Philadelphia positive ALL.
• Mature B-ALL.
• Mixed phenotype acute leukemia.
• Any previous treatment with cytotoxic chemotherapy excluding treatment for TAM orradiation therapy. Patient pre-treated with short term steroid (< 7 days of durationwithin last 1 month prior to treatment start) can be enrolled into this study.
• Renal dysfunction with creatinine >2x upper limit of normal (ULN). Patients whosecreatinine has improved to <2x ULN before treatment commencement can enrol subject todiscretion of site PI.
• Liver dysfunction with direct bilirubin > 5x ULN.
• Any serious uncontrolled medical condition or impending end organ dysfunction thatwould impair the ability of the subject to receive protocol therapy, including:

1. History of coronary arterial disease, cardiomyopathy, heart failure, arrhythmia (other than sinus arrhythmia) or severe cardiac malformation which with residualabnormalities or requires further major corrective surgery within 2 years.
2. Ongoing uncontrolled hypertension.
3. Ongoing uncontrolled diabetes mellitus.
4. Ongoing uncontrolled infection.
5. History of congenital or acquired immunodeficiency including HIV infection.
6. History of interstitial pneumonia, pulmonary fibrosis, bronchiectasis or severepulmonary emphysema.
7. CNS hemorrhage.
8. Psychiatric disorder.
9. Other concurrent active neoplasms.

• Pregnant or lactating women.
• Doubtful compliance or ability to complete study therapy due to financial, social,familial or geographic reason, or in the judgement of site investigator.